Polyfunctional IL-21 IFNG T follicular helper cells contribute to checkpoint inhibitor diabetes mellitus and can be targeted by JAK inhibitor therapy.

Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy, but their use is limited by the development of autoimmunity in healthy tissues as a side effect of treatment. Such immune-related adverse events (IrAE) contribute to hospitalizations, cancer treatment interruption and even premature death. ICI-induced autoimmune diabetes mellitus (ICI-T1DM) is a life-threatening IrAE that presents with rapid pancreatic beta-islet cell destruction leading to hyperglycemia and life-long insulin dependence.

Standardized List Evaluating Apnea (SLEAP): A Comprehensive Survey to Define the Quality of Life in OSA.

Objective: To develop and validate a patient-reported outcome measure (PROM) to evaluate the quality of life (QoL) among patients with obstructive sleep apnea (OSA).

Study Design: A prospective cohort study.

Settings: Tertiary referral center.

Transendoscopic laser ablation of an esophageal plasma cell tumor in a cat.

Case Summary: A 15-year-old male castrated domestic shorthair cat was presented for acute lethargy, vomiting and hyporexia. Abdominal and thoracic radiographs revealed a caudal thoracic/esophageal soft tissue opacity with concern for an esophageal mass or an esophageal foreign body. Esophagoscopy confirmed the presence of a large, irregular, mid-esophageal mass.

NCCN Guidelines® Insights: Management of Immunotherapy-Related Toxicities, Version 2.2024.

The NCCN Guidelines for the Management of Immunotherapy-Related Toxicities are intended to provide oncology practitioners with guidance on how to manage the wide-ranging and potentially fatal toxicities that may occur with cancer immunotherapy. The guidelines address immune-related adverse events related to immune checkpoint inhibitors, CAR T-cell therapies, and lymphocyte engagers (which include T-cell-engaging bispecific antibodies). These NCCN Guidelines Insights highlight recent guideline updates pertaining to the management of emerging toxicities related to cancer immunotherapy.

Universal penalized regression (Elastic-net) model with differentially methylated promoters for oral cancer prediction.

Background: DNA methylation showed notable potential to act as a diagnostic marker in many cancers. Many studies proposed DNA methylation biomarker in OSCC detection, while most of these studies are limited to specific cohorts or geographical location. However, the generalizability of DNA methylation as a diagnostic marker in oral cancer across different geographical locations is yet to be investigated.

Experiences of women sexual assault survivors with police in the early aftermath of assault: Results from a large-scale prospective study.

Over 100,000 women present for emergency care after sexual assault (SA) annually in the United States. To our knowledge, no large prospective studies have assessed SA survivor experiences with police. Women SA survivors enrolled at 13 sites ( = 706), and 630 survivors reported on their police interactions.

Transforming care for pregnancy loss: A qualitative study on advancing practices and addressing existing needs.

Recent years have seen significant growth in the body of knowledge and the development of guidelines on pregnancy loss. This qualitative study analyses how these advancements have been implemented with a focus on health literacy, hospital protocols, and societal responses. Thematic analysis of semi-structured interviews from bereaved parents (n = 11) and healthcare professionals (n = 7) in Italy uncovers significant lapses in health literacy and societal reluctance to address pregnancy loss, which obstructs informed parental decision-making.

Research with women sexual assault survivors presenting for emergency care is safe: Results from a multi-site, prospective observational cohort study.

A barrier to research with sexual assault survivors is the concern that research participation might be a negative experience for participants. We report the experiences with research of adult women sexual assault survivors participating in a large-scale, multi-site, prospective observational study that enrolled participants at the time of presentation for emergency care. Participants (n = 706, M = 28 years of age; 57% white, 15% Black) self-reported their experience with research 1 week, 6 weeks, 6 months, and 1 year post-assault.

A pathologically expanded, clonal lineage of IL-21-producing CD4+ T cells drives inflammatory neuropathy.

Inflammatory neuropathies, which include chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain Barré syndrome (GBS), result from autoimmune destruction of the PNS and are characterized by progressive weakness and sensory loss. CD4+ T cells play a key role in the autoimmune destruction of the PNS. Yet, key properties of pathogenic CD4+ T cells remain incompletely understood.

A Look Inside-Histopathological Examinations of Different Tail Tip Lesions in Dairy Cows.

Feedlot cattle are frequently affected by inflammation and necrosis of the tail tips, resulting in impeded animal welfare and economic losses. In a recent study, it was demonstrated that dairy cows are also affected by different lesions of the tail tip, including alopecia, annular constrictions, crusting, scaling and swelling. Despite the frequent occurrence of these lesions, the underlying etiology and pathomechanisms are unclear to date.

The Effect of Apalutamide on Thyroid Function in Prostate Cancer Patients.

Context: Apalutamide (APT) is a nonsteroidal antiandrogen medication used to treat metastatic castrate-sensitive and nonmetastatic castrate-resistant prostate cancer. Early clinical trials of APT identified thyroid dysfunction as a common adverse effect of therapy, but the clinical presentation and management of APT-induced hypothyroidism has not been studied.

Objective: The objective of our study is to elucidate the clinical presentation and treatment approach of APT-associated thyroid dysfunction in prostate cancer patients.

Impact of neighborhood disadvantage on posttrauma outcomes after sexual assault.

In the United States, 8,000,000 people seek emergency care for traumatic injury annually. Motor vehicle collisions (MVCs) and sexual assault are two common sources of trauma, with evidence that reduced neighborhood-level socioeconomic characteristics increase posttraumatic pain and stress after an MVC. We evaluated whether neighborhood disadvantage was also associated with physical and mental posttrauma outcomes after sexual assault in a sample of adult women (N = 656) who presented for emergency care at facilities in the United States following sexual assault and were followed for 1 year.

Using unstructured crowd-sourced data to evaluate urban tolerance of terrestrial native animal species within a California Mega-City.

In response to biodiversity loss and biotic community homogenization in urbanized landscapes, there are increasing efforts to conserve and increase biodiversity within urban areas. Accordingly, around the world, previously extirpated species are (re)colonizing and otherwise infiltrating urban landscapes, while other species are disappearing from these landscapes. Tracking the occurrence of traditionally urban intolerant species and loss of traditionally urban tolerant species should be a management goal of urban areas, but we generally lack tools to study this phenomenon.

Code generation in ORCA: progress, efficiency and tight integration.

An improved version of ORCA's automated generator environment (ORCA-AGE II) is presented. The algorithmic improvements and the move to C++ as the programming language lead to a performance gain of up to two orders of magnitude compared to the previously developed PYTHON toolchain. Additionally, the restructured modular design allows for far more complex code engines to be implemented readily.

Development of a brief bedside tool to screen women sexual assault survivors for risk of persistent posttraumatic stress six months after sexual assault.

This study aims to develop and validate a brief bedside tool to screen women survivors presenting for emergency care following sexual assault for risk of persistent elevated posttraumatic stress symptoms (PTSS) six months after assault. Participants were 547 cisgender women sexual assault survivors who presented to one of 13 sexual assault nurse examiner (SANE) programs for medical care within 72 h of a sexual assault and completed surveys one week and six months after the assault. Data on 222 potential predictors from the SANE visit and the week one survey spanning seven broadly-defined risk factor domains were candidates for inclusion in the screening tool.

One-Tip enables comprehensive proteome coverage in minimal cells and single zygotes.

Mass spectrometry (MS)-based proteomics workflows typically involve complex, multi-step processes, presenting challenges with sample losses, reproducibility, requiring substantial time and financial investments, and specialized skills. Here we introduce One-Tip, a proteomics methodology that seamlessly integrates efficient, one-pot sample preparation with precise, narrow-window data-independent acquisition (nDIA) analysis. One-Tip substantially simplifies sample processing, enabling the reproducible identification of >9000 proteins from ~1000 HeLa cells.

Notch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization.

Sustained Notch2 signals induce trans-differentiation of Follicular B (FoB) cells into Marginal Zone B (MZB) cells in mice, but the physiology underlying this differentiation pathway is still elusive. Here, we demonstrate that most B cells receive a basal Notch signal, which is intensified in pre-MZB and MZB cells. Ablation or constitutive activation of Notch2 upon T-cell-dependent immunization reveals an interplay between antigen-induced activation and Notch2 signaling, in which FoB cells that turn off Notch2 signaling enter germinal centers (GC), while high Notch2 signaling leads to generation of MZB cells or to initiation of plasmablast differentiation.